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Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box–Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to “wrap” them will be minimized.

Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment.

The Chelonaplysilla genus possesses a numerous bioactive diterpenes with antiinflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC 50 value 16.5 ± 0.8 μg/mL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC 50 = 2.8 ± 0.03 μg/mL). Among the dereplicated compounds, macfarlandin F ( 16) and pourewanone ( 25) demonstrated the highest potential with co-crystallized ligand 63O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications. Experimental Sponge materialThe marine sponge Chelonaplysilla erecta was collected by Prof. D. Hajjar and A. A. Makki, from the Red Sea, Jeddah side. The sponge possessed an upright growing skeleton with long and thick spongin fibres. Characteristically, the dendritic fibres anastomose frequently with each other in agreement with previous literature (Tsurnamal 2013). The specimens were washed then with 1% phosphate buffered saline (PBS), immediately on the boat. The specimens with their label were wrapped in aluminium foil and placed on ice, then stored at -80 °C until further processing. The specimen's surface peel was removed and immersed in xylene for 24 hours. DPX (Dibutyl Phthalate Polystyrene Xylene) was used to mount a permanent slide of the peel. Under a stereo microscope, a single fibre with its base and branches intact was extracted from the sponge for species identification. Sponge samples were identified by Prof. Dr. El-Sayd Abed El-

Introduction Sponge- Coscinoderma sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable. Methodology In the present study, the metabolomic profiling of Coscinoderma sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). Coscinoderma- derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively). Results The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds 1 – 15 ) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC 50 values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC 50 values ranged from 1.7 to 4.1 µg/mL). Discussion Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.